Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBPα.

The CCAAT enhancer-binding protein α (C/EBPα) plays an important role in myeloid cell differentiation and in the enhancement of C/EBPα expression/activity, which can lead to granulocytic differentiation in acute myeloid leukemia (AML) cells. We found that styryl quinazolinones induce upregulation of C/EBPα expression, and thereby induce myeloid differentiation in human myeloid leukemia cell lines. We screened a series of active styryl quinazolinones and evaluated the structure⁻activity relationship (SAR) of these small molecules in inducing C/EBPα expression-thereby prompting the leukemic cells to differentiate. We observed that compound 78 causes differentiation at 3 µM concentration, while 1 induces differentiation at 10 µM concentration. We also observed an increase in the expression of neutrophil differentiation marker CD11b upon treatment with 78. Both the C/EBPα and C/EBPε levels were found to be upregulated by treatment with 78. These SAR findings are inspiration to develop further modified styryl quinazolinones, in the path of this novel differentiation therapy, which can contribute to the care of patients with AML.

Cardiogenic differentiation of mesenchymal stem cells with gold nanoparticle loaded functionalized nanofibers.

Cardiac tissue engineering promises to revolutionize the treatment of patients with end-stage heart failure and provide new solutions to the serious problems of shortage of heart donors. The influence of extracellular matrix (ECM) plays an influential role along with nanostructured components for guided stem cell differentiation. Hence, nanoparticle embedded Nanofibrous scaffolds of FDA approved polycaprolactone (PCL), Vitamin B12 (Vit B12), Aloe Vera(AV) and Silk fibroin(SF) was constructed to differentiate mesenchymal stem cells into cardiac lineage. Cardiomyocytes (CM) and Mesenchymal stem cells (MSC) were co-cultured on these fabricated nanofibrous scaffolds for the regeneration of infarcted myocardium. Results demonstrated that synthesized gold nanoparticles were of the size 16 nm and the nanoparticle loaded nanofibrous scaffold has a mechanical strength of 2.56 MPa matching that of the native myocardium. The gold nanoparticle blended PCL scaffolds were found to be enhancing the MSCs proliferation and differentiation into cardiogenesis. Most importantly the phenotype and cardiac marker expression in differentiated MSCs were highly resonated in gold nanoparticle loaded nanofibrous scaffolds. The appropriate mechanical strength provided by the functionalized nanofibrous scaffolds profoundly supported MSCs to produce contractile proteins and achieve typical cardiac phenotype.

Curcumin- and natural extract-loaded nanofibres for potential treatment of lung and breast cancer: in vitro efficacy evaluation.

Drug-eluting medical implants are more common, particularly for fighting against cancers. FDA and other drug regulatory bodies have approved many nanoformulated devices eluting active pharmaceutical ingredients and thus there is growing demand for further value- added devices. Nanofibre membranes are known for its versatility of drug incorporation and sustained drug release. We intend to fabricate natural ingredient or extract, and their combination loaded polycaprolactone (PCL) nanofibre for usage as drug-eluting stents or implants for anticancer activity against lung and breast cancers. The fabricated nanofibre membranes were characterised by scanning electron microscope for morphology, FT-IR for chemical nature and tensile testing for mechanical strengths. Release of curcumin was studied with time to find the applicability of the device as drug-eluting implant. The activity of the nanofibre membranes was tested against human breast cancer (MCF7) and lung cancer (A459) cell lines in vitro. In both the cell lines tested, 1% aloe vera and 5% curcumin-loaded PCL nanofibre exhibited 15% more cytotoxicity in comparison with the commercial drug 1% cis-Platin-loaded PCL nanofibre after 24 h incubation.

Gold nanoparticle loaded hybrid nanofibers for cardiogenic differentiation of stem cells for infarcted myocardium regeneration.

Heart disease is the leading cause of mortality in many industrialized nations and is often related to irregularities in electrical function that can radically damage cardiac functioning. The aim of this study is to develop a novel therapeutic hybrid scaffold that can couple electrical, mechanical, and biological properties, desirable for cardiac tissue regeneration. BSA/PVA scaffolds are fabricated in the ratio 2:1 and gold nanoparticles (AuNPs) embedded scaffolds in the ratios BSA/PVA/Au of 2:1:0.1 (lower concentration) and BSA/PVA/Au of 2:1:0.4 (higher concentration) by electrospinning. The scaffolds are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle, Fourier transform infrared (FTIR) spectroscopy, and tensile testing to analyze the fiber morphology, AuNP distribution, hydrophilicity, surface functional groups, and mechanical properties of the scaffolds, respectively. Results show that ex vivo pretreatment of MSCs using 5-aza and AuNPs loaded conductive nanofibrous construct could lead to enhanced cardiomyogenic differentiation and result in superior biological and functional effects on infarcted myocardium regeneration.

Electrospun inorganic and polymer composite nanofibers for biomedical applications.

Engineered nanofibers are generally focused on filtration, solar cells, sensors, smart textile fabrication, tissue engineering, etc. Electrospun nanofibers have potential advantages in tissue engineering and regenerative medicine, because of the ease in the incorporation of drugs, growth factors, natural materials, and inorganic nanoparticles in to these nanofiber scaffolds. Electrospun nanofiber scaffolds composed of synthetic and natural polymers are being explored as scaffolds similar to natural extracellular matrix for tissue engineering. The requirement of the inorganic composites in the nanofiber scaffolds for favouring hard and soft tissue engineering applications is dealt in detail in the present review. Regarding drug delivery applications of the composite nanofibers, the review emphasizes on wound healing with silver nanoparticles incorporated nanofibers, bone tissue engineering, and cancer chemotherapy with titanium and platinum complexes loaded nanofibers. The review also describes gold nanoparticle loaded nanofibers for cancer diagnosis and cosmetic applications.

Mimicking native extracellular matrix with phytic acid-crosslinked protein nanofibers for cardiac tissue engineering.

A functional scaffold fabricated is developed from natural polymers, favoring regeneration of the ischemic myocardium. Hemoglobin/gelatin/fibrinogen (Hb/gel/fib) nanofibers are fabricated by electrospinning and are characterized for morphology, scaffold composition, functional groups and hydrophilicity. It is hypothesized that ex vivo pretreatment of mesenchymal stem cells (MSCs) using 5-azacytidine and such a functional nanofibrous construct having a high oxygen-carrying potential could lead to enhanced cardiomyogenic differentiation of MSCs and result in superior biological and functional effects. The combination of a functional nanofibrous scaffold composed of natural polymers and crosslinked with a natural crosslinking agent, phytic acid, and stem cell biology may prove to be a novel therapeutic device for treatment of myocardial infarction.

Minimally invasive injectable short nanofibers of poly(glycerol sebacate) for cardiac tissue engineering.

Myocardial tissue lacks the ability to appreciably regenerate itself following myocardial infarction (MI) which ultimately results in heart failure. Current therapies can only retard the progression of disease and hence tissue engineering strategies are required to facilitate the engineering of a suitable biomaterial to repair MI. The aim of this study was to investigate the in vitro properties of an injectable biomaterial for the regeneration of infarcted myocardium. Fabrication of core/shell fibers was by co-axial electrospinning, with poly(glycerol sebacate) (PGS) as core material and poly-L-lactic acid (PLLA) as shell material. The PLLA was removed by treatment of the PGS/PLLA core/shell fibers with DCM:hexane (2:1) to obtain PGS short fibers. These PGS short fibers offer the advantage of providing a minimally invasive injectable technique for the regeneration of infarcted myocardium. The scaffolds were characterized by SEM, FTIR and contact angle and cell-scaffold interactions using cardiomyocytes. The results showed that the cardiac marker proteins actinin, troponin, myosin heavy chain and connexin 43 were expressed more on short PGS fibers compared to PLLA nanofibers. We hypothesized that the injection of cells along with short PGS fibers would increase cell transplant retention and survival within the infarct, compared to the standard cell injection system.